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Antiresorptive Medications and Medication Related Osteonecrosis of the Jaw: Part II

Published on: Jun 15, 2022
 By: Dr. Anthony S. Feck
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Oral surgical procedures necessitate some degree of trauma to the bone in the upper and lower jaws. When the patient is taking prescribed medications that impact how bone heals after dental surgery, the potential for medication-related osteonecrosis of the jaw (MRONJ) exists. 

In Part I of this article, I explored the pathogenesis of MRONJ, as well as the predominant categories of drugs associated with this condition. In Part II, I cover patient assessment and methods to prevent its occurrence.

Risk Factors

Risk associated with MRONJ involves six factors (see Table 1):

  1. Dose of medication and method of administration. High doses of IV antiresorptive medications (generally prescribed to treat cancer) pose a higher risk than low dose IV or PO bisphosphonates (generally prescribed to treat osteoporosis).  Specifically:

    -When cancer patients are treated with the IV bisphosphonate zolendronate (Zometa), or the Subcutaneous RANK-L Inhibitor denosumab (Xgeva), the incidence of MRONJ after oral surgery increases 10 to 100 fold relative to no antiresorptive medication, while the risk among cancer patients exposed to the antiangiogenic agent bevacizumab (Avastin) increases the incidence 10 fold. The combination of antiangiogenic agents with bisphosphonates markedly increases the risk.

    -Among osteoporotic patients being treated with oral bisphosphonates, such as alendronate (Fosamax, Fosamax D), risedronate (Actonel), and ibandronate (Boniva), the risk of MRONJ after oral surgery is 0.1% or less. Likewise, IV bisphosphonates such as zoledronic acid (Reclast) and the subcutaneous administered RANK-L Inhibitor denosumab (Prolia) are associated with a low risk.

  2. Duration of medication exposure. In general, risk increases progressively with duration of therapy.

  3. Type of surgery. Tooth extraction is the precipitating factor in 52% to 61% of cases. In cancer patients exposed to IV antiresorptive medications, tooth extraction is associated with a 33-fold increase for MRONJ.

  4. Anatomical factors. MRONJ is more likely to occur in the mandible (73%) than in the maxilla (22.5%), but can occur in both jaws (4.5%).

  5. Inflammation and infection. Among cancer patients with MRONJ, pre-existing inflammatory dental disease is a risk factor in 50% of the cases.  Denture use is associated with a 2-fold increased risk for MRONJ in cancer patients treated with IV antiresorptive medications.

  6. Other factors. Drugs that reduce the inflammatory response (eg. corticosteroids), and medical conditions that make patients more prone to infection (eg. diabetes mellitus), are considered contributing risk factors for MRONJ.  Social factors, like tobacco use, that result in compromised vascularity also may play a role.

The C-terminal Telopeptide (CTX) is not validated and not recommended as a metric for risk stratification.

Table 1. MRONJ Risk Factors Relative to Antiresorptive Medications, Ranked By Degree of Risk 


Increased Risk

 Decreased Risk

High Doses       

Low Doses

Intravenous Administration

Oral Administration

Greater Than 4 yrs. Duration   

Less Than 4 yrs. Duration

More Traumatic Procedure      

Less Traumatic Procedure

Lower Jaw                      

Upper Jaw


No Inflammation/Infection

Anti-inflammatory Meds

No Anti-inflammatory Meds

Prone to Infection

Not Prone to Infection

Identifying Patients at Risk – The Health Questionnaire

The first step is to discover if patients have taken or are currently taking an antiresorptive medication. Patients tend to recognize drug names and medical conditions, but not classes of medications. Therefore, it is prudent to include these questions in the health history questionnaire:

  1. Are you currently on or have you ever been on any of the following medications?

    Fosamax                                                        Zometa

    Fosamax plus D                                          Aredia

    Actonel                                                          Prolia

    Boniva                                                           Xgeva

    Prolia                                                             Avastin

  2. If you answered yes:

    a. How long have you been taking (or how long did you take) this medication?

    b. What was the dose of the medication?

    c. If you are no longer on the medication, how long has it been since discontinuation?

  3. Do you have or have you had any kind of cancer?

    a. What type of cancer?

    b. Have you been treated with chemotherapy?

    c. What type of chemotherapy have you had?

Any incomplete information regarding medications and their dosages can be determined by a medical consult.

Recommendations for Patients Being Treated for Osteoporosis

For patients taking bisphosphonates for osteoporosis, the risk more than doubles if they have been exposed to the medication for more than four years. Other factors that increase risk are advanced age (older than 65), oral infections, pre-existing dental disease, diabetes mellitus, steroid use, and head and neck radiation. Alcohol and tobacco use may be contributing factors as well.

Patients with more than four years of therapy with or without other clinical risks should be informed of the small risk of osteonecrosis. They should be instructed in good oral hygiene and regular dental care. Non-surgical options including the aggressive use of antibiotics should be considered if infection exists. Even though no data supports a drug holiday, the interruption of bisphosphonate therapy should be considered two months before treatment, and resumed once osseous healing has occurred.

Patients with less than four years of therapy and no other clinical risks should be informed the risk of MRONJ is very small but cannot be completely eliminated.  For these patients, as with all patients taking antiresorptive medications, good oral hygiene and regular dental care should be stressed. There is no alteration or delay in any planned dental treatment for these patients.

Recommendations for Patients Being Treated for Cancer

If patients have taken or are taking an IV antiresorptive medication to treat cancer, they should be informed of the risks of treatment as well as the risks of no treatment. Good oral hygiene and regular dental care should be stressed to prevent and limit invasive treatment. If infection is present, the aggressive use of antibiotics as well as chlorhexidine rinse should be considered. Endodontic procedures are preferred over extractions. If an extraction is necessary, atraumatic methods should be adhered to. There is no data on the efficacy of a drug holiday. 

A thorough examination and radiographic assessment should be performed before cancer patients begin taking IV Bisphosphonates, and any oral surgical procedures, periodontal treatment, or corrections for ill-fitting dentures should be addressed before initiation of antiresorptive medication treatment. Compromised teeth should be eliminated, and preventive measures instituted.


The past few years have seen the introduction of new medications designed to address the loss of bone density caused by osteoporosis and some forms of cancer. In addition, other medications are now available to reduce vascularization required for tumor growth. These medications can impact normal bone healing, resulting in osteonecrosis of the jaws after dental surgery, a condition that can be accompanied by significant morbidity. Dentists must be aware of these medications, their potential to cause MRONJ, and employ methods to avoid the condition.  

Dr. Anthony Feck has 36 years of private practice experience and an extensive background in sedation in dentistry. As one of the founders of DOCS Education, he now serves as Dean of Faculty. Dr. Feck has taught dentists and team members from all over the world how to safely and effectively treat high fear patients with conscious sedation. Dr. Feck also has developed a reputation as a leader in dental implantology education, serving as a clinical instructor for Little Implant Co. In 2005, Dr. Feck founded Sunrise Dental Solutions (SDS), a practice optimization company. He practices in a multi-doctor office in Lexington, Kentucky, that concentrates on sedation, dental implantology and dental-facial cosmetics.

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